High rates of fuel consumption are not required by insulating motifs to suppress retroactivity in biochemical circuits

Abhishek Deshpande; Thomas E. Ouldridge

High rates of fuel consumption are not required by insulating motifs to suppress retroactivity in biochemical circuits

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Author(s): Abhishek Deshpande^{1, 2} and Thomas E. Ouldridge³
- Affiliations: 1: Department of Mathematics , Imperial College London , London SW7 2AZ , UK ;
  2: School of Technology and Computer Science , Tata Institute of Fundamental Research , Mumbai 400005 , India ;
  3: Department of Bioengineering , Imperial College London , London SW7 2AZ , UK
Source: Volume 1, Issue 2, December 2017, p. 86 – 99
DOI: 10.1049/enb.2017.0017 , Online ISSN 2398-6182

This is an open access article published by the IET under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/)

Received 09/08/2017, Accepted 31/10/2017, Revised 18/10/2017, Published 14/12/2017

Retroactivity arises when the coupling of a molecular network $U$ to a downstream network $D$ results in signal propagation back from $D$ to $U$ . The phenomenon represents a breakdown in modularity of biochemical circuits and hampers the rational design of complex functional networks. Considering simple models of signal-transduction architectures, the authors demonstrate the strong dependence of retroactivity on the properties of the upstream system, and explore the cost and efficacy of fuel-consuming insulating motifs that can mitigate retroactive effects. They find that simple insulating motifs can suppress retroactivity at a low fuel cost by coupling only weakly to the upstream system $U$ . However, this design approach reduces the signalling network's robustness to perturbations from leak reactions, and potentially compromises its ability to respond to rapidly varying signals.

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High rates of fuel consumption are not required by insulating motifs to suppress retroactivity in biochemical circuits

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